Granzyme B-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic T cells modifies cytoskeleton dynamics

Granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic T lymphocytes (Tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. Based on the notion that many gzms, including A, B, C, K, H, and M exhibit cytotox...

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Hauptverfasser: Martin, Praxedis Sina (VerfasserIn) , Pardo, Julián (VerfasserIn) , Schill, Natalie (VerfasserIn) , Jöckel, Lars (VerfasserIn) , Berg, Matthias (VerfasserIn) , Froelich, Christopher J. (VerfasserIn) , Wallich, Reinhard (VerfasserIn) , Simon, Markus M. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2010
In: The journal of biological chemistry
Year: 2010, Jahrgang: 285, Heft: 24, Pages: 18918-18927
ISSN:1083-351X
DOI:10.1074/jbc.M109.056028
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M109.056028
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Verfasserangaben:Praxedis Martin, Julián Pardo, Natalie Schill, Lars Jöckel, Matthias Berg, Christopher J. Froelich, Reinhard Wallich, and Markus M. Simon

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520 |a Granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic T lymphocytes (Tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. Based on the notion that many gzms, including A, B, C, K, H, and M exhibit cytotoxic activity in vitro, all gzms are believed to serve a similar function in vivo. However, more recent evidence supports the concept that gzms are not unidimensional but, rather, possess non-cytotoxic potential, including stimulation of pro-inflammatory cytokines and anti-viral activities. The present study shows that isolated mouse gzmB cleaves the actin-severing mouse protein, cytoplasmic gelsolin (c-gelsolin) in vitro. However, when delivered to intact target cells by ex vivo immune Tc cells, gzmB mediates c-gelsolin proteolysis via activation of caspases 3/7. The NH(2)-terminal c-gelsolin fragment generated by either gzmB or caspase 3 in vitro constitutively severs actin filaments without destroying the target cells. The observation that gzmB secreted by Tc cells initiates a caspase cascade that disintegrates the actin cytoskeleton in target cells suggests that this intracellular process may contribute to anti-viral host defense. 
650 4 |a Animals 
650 4 |a Apoptosis 
650 4 |a Caspase 3 
650 4 |a CD8-Positive T-Lymphocytes 
650 4 |a Cytoskeleton 
650 4 |a Fibroblasts 
650 4 |a Gelsolin 
650 4 |a Granzymes 
650 4 |a Lymphocytic choriomeningitis virus 
650 4 |a Mice 
650 4 |a Microscopy, Fluorescence 
650 4 |a Models, Biological 
650 4 |a RNA, Messenger 
650 4 |a T-Lymphocytes, Cytotoxic 
650 4 |a Transcription, Genetic 
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